JPS59144792A - 3-(beta-chloroethylureide)propyl triethoxy silane - Google Patents

Abstract

NEW MATERIAL:3-(beta-Chloroethylureido)propyltriethoxysilane. USE:A starting material for producing polysilsesquioxane, a carcinostatic agent. PREPARATION:The reaction between 3-aminopropyltriethoxysilane and beta-chlroethyl isocyanate gives the objective compound.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel compound, 5-(β-chloroethylureido)propyltriethoxysilane.

The present inventor has synthesized various polysilsesquioxanes and conducted various studies on their physiological activities. As a result, a new compound, 3-(β-chloroethylureido)propyltriethoxysilane, and a new polysilsesquioxane derived from it were synthesized, and the polysilsesquioxane has excellent biological activity, In particular, it was confirmed that it has anticancer activity, and the present invention was completed.

The 3-(β-chloroethylureido)propyltriethoxysilane of the present invention is 1 (01130H20)3SiOH2cH3c'a2NH
ONEca20H2cz is a novel compound represented by the formula (1). The manufacturing method is not particularly limited, and for example, a method of reacting 3-aminopropyltriethoxysilane and β-chloroethyl isocyanate, a method of reacting 3-isocyanatopropyltriethoxysilane and β-chloroethylamine, etc. Can be mentioned. Generally, these reactions proceed quantitatively under anhydrous conditions even at room temperature.

3-(β-chloroethylureido) represented by formula (1)
Propyltriethoxysilane is a white crystalline solid with a low melting point, and its structure can be confirmed by the following methods (a) to (c).

(b) By measuring the infrared absorption spectrum, 3
The presence of NH group, which shows strong absorption at 400 in-', and the presence of ureido carbonyl group, which shows strong characteristic absorption at 1705 fi-1, was determined by the known weight f%, and then the weight i% of each recognized element. By subtracting the sum from 100, the weight of the oxygen element i:h can be calculated, and the compositional formula of the product can therefore be determined.

(c) By measuring the 13C-nuclear magnetic resonance spectrum, the number of carbon atoms in the compound, the arrangement of carbon chains, and the bonding mode of carbon atoms can be determined. That is, the measured spectrum has a chemical shift value (δ, ppm
) 19.7.59.7,? , 6.22.4.52.1
(overlapping), 4368, and the chemical shift values and intensities indicate that three ethyl groups, one carbon atom directly bonded to a silicon atom, and an NH group, as shown in the examples below. The presence of two carbon atoms adjacent to , one carbon atom directly connected to the chlorine atom, and one carbon atom sandwiched between the aiiz groups can be confirmed.

By hydrolyzing the 6-(β-chloroethylureido)furobyltriethoxysilane of the present invention, it can be easily converted into chloroethylureidoprobilbolysilsesquioxane represented by the general formula: The above-mentioned polysilsesquioxane has significantly superior physiological activity compared to known polysilsesquioxanes, and is an excellent compound that exhibits particularly excellent anticancer activity. Therefore, the compound provided by the present invention is extremely useful as a raw material for the above-mentioned polysilsesquioxane.

EXAMPLES Below, Examples and Reference Examples will be shown to explain the present invention more clearly, but the present invention is not limited to these Examples.

Example 1 Method for producing 5-(β-chloroethylureido)furobyltriethoxysilane.

Distilled purified 3-aminopropyltriethoxysilane (
21,00g, 95 mmols) of anhydrous hekiza/
solution (β-chloroethyl isocyanate (1
When 1,00 g, 104 mmole) was added dropwise under magnetic stirring, the reaction started with mild heat generation.

After the dropwise addition was completed, the reaction solution was heated on a hot water bath for one hour. After removing low boilers by distillation, the residue was heated on an oil bath (approximately 100°C
) to obtain a colorless viscous substance, which became white crystals (28.70 g) upon standing. When its infrared absorption spectrum was measured, it showed an absorption based on NH at 3400σ-1 and a strong absorption based on ureido carbonyl at 1705α-1. Its elemental analysis values were H8.10chi, 041.71chi, c+t11.89chi [, O,
,H! Calculated values for the composition formula of 7N2040zSi (326,91) H8.33%, C44,09chi,
H8, 57%, O/=10.85, in good agreement with -5=. Further, the analysis results of I3□-nuclear magnetic resonance spectrum (J, ppm: tetramethylsilane standard) were as follows.

1 From the above results, it became clear that the isolated product was 3-(β-chloroethylureido)propyltriethoxysilane. The yield was 92.5% (88 mmole) based on the 3-aminopropyltriethoxysilane used.
)Met.

Reference example: Water (701
After stirring for two nights, low-boiling substances were removed by distillation, and the residue was vacuum-dried on an oil bath (approximately 70°C) for -1 day to obtain a white solid (s7.63 g). When the infrared absorption spectrum of this solid was measured, it was found that 33[IQ
NH-based absorption and 17051m in crn-'
-' showed strong absorption based on ureido carbonyl.

Its elemental analysis values are N5.75chi, 050.72chi, N1
2.45%, at15.91%, 3-(β-chloroethylureido)propylpolysilsesquioxane monohydrate (06H1jlN20□, 5ata1・N2
H6.04 which is the calculated value for 0), a 30.8
5 q6 N M 11-99%, cJ15.1796
It matched well. Furthermore, the white solid was dissolved in a small amount of water and the +"O- nuclear magnetic resonance spectrum was measured using tetramethylsilane as a standard. The results were as follows (values are δ, ppm
).

1 From the above results, it became clear that the obtained white solid was 3-(β-chloroethylureido)propyl polysilsesquioxane. The yield was almost quantitative.

Then, the obtained 3-(β-chloroethylureido)
Propylpolysilsesquioxane was added to a saline solution containing the surfactant Tween 80 and a specified amount of the sample was added to the sample.
Type 1 sample solution (616111i+/KP, 199 m
g/Kps 15811g/KP, 12 6 Tomi g
/Ky, 1 omg /KP,
7 q shoulder g / li, 6 3
Q/KP, 40 mg/su) was prepared. This sample solution was intraperitoneally injected into 36 male and 8 female 0DFI mice weighing around 201 kg and tested for 20 days. For the determination, a sample solution containing a specified amount of the sample was prepared by adding each 112 thylureido)propyl polysilsesquioxane to a physiological saline solution containing the surfactant Tween 80. The sample solution was divided into 5 x 106 Ehrlich cancer cells.
Intraperitoneally into 6 Swiss mice (male) with 0.5
ml was continuously injected for 9 days. From the results of the survival effect over 60 days, the mean survival days (MST) was calculated and compared with the mean survival days of the control group (30 animals).
/. We calculated Chi. That is, the average survival days were determined for the test subject (T) and the control subject (0), and calculated as T10 x 100 days). The results are shown in Table 1.

Margin below 9- -10-

Claims (1)

[Claims] (1) 3-(β-chloroethylureido)furobyltriethoxysila/